Cristal Therapeutics has developed a pioneering approach to transform drugs into tailor-made nanoparticles via its proprietary polymeric technology, registered as CriPec®. The CriPec platform consists of tuneable polymers and biodegradable drug linkers that allows for the rational design and straightforward manufacturing of custom-made nanomedicines.
Assembly of the CriPec nanoparticles
CriPec nanomedicines are assembled as illustrated by the presented scheme:
- Derivatisation of a drug molecule with a linker.
- The tailor-made CriPec polymer self-assembles with the drug-linker into polymeric micelles.
- Immediate crosslinking of both the CriPec polymer and the drug-linker results in transiently stable nanoparticles.
- Purification via a straightforward process.
The prolonged circulation is obtained by the polyethyleneglycol (PEG) stealth layer that forms the surface of the particle, and which prevents rapid elimination of the nanoparticles from the bloodstream. This prolonged circulation results in a higher accumulation at the diseased tissue. The biological behaviour of CriPec nanomedicines is dependent on the conformation of the nanoparticle itself and not affected by the type of entrapped drug molecules, thereby making the behaviour of CriPec nanoparticles very predictable.
Customized drug release
The proprietary class of linkers that temporarily entraps the drug within the CriPec nanoparticle determines the site and rate of release of the native drug molecule. The example below demonstrates how the drug release can be achieved via solely adjusting the type of linker, as all other properties of the nanomedicines were kept constant. Importantly, drug release can be customized and is only induced by chemically-induced cleavage. No enzymes are involved, so the release profile in vitro is equal to the pattern in vivo. The nanoparticles are degraded following the release of the drug.
The extensive flexibility in the CriPec polymers results in a wide range of advantageous features, such as control over the size, the biodegradability profile as well as the ability to conjugate ligands to the surface.
Most drug molecules including hydrophilic and hydrophobic small molecules as well as (large) peptides can be combined with the CriPec polymers to generate custom-made nanomedicines.
Cristal Therapeutics has already developed a generic GMP manufacturing process for its CriPec nanomedicines. The process steps are independent of the entrapped drug. Nanoparticles can be prepared as small as 30 nm up to at least 100 nm, in all cases with a very narrow size distribution. With the CriPec process an excellent yield and high drug loading is obtained. The nanoparticles can be sterilized by aseptic filtration.
Because of the stability of the nanoparticles, the CriPec nanomedicines can be administered intravenously and subcutaneously. Due to the conjugation of the drug to the particle no local side effects are obtained following s.c. injection.